Polypeptides, such as enzymes, antibodies, hormones, cytokines, etc., are tremendously useful as therapeutic agents. However, routes for systemically introducing such polypeptides to a subject are limited. Oral administration of the polypeptides is typically not feasible, as the polypeptides are either degraded in the gastrointestinal tract or are blocked from reaching the bloodstream. Direct intravenous administration is therefore the major route by which polypeptides are systemically introduced.
Certain types of genetically engineered bacteria have been used as vehicles for locally delivering polypeptides to various tissues. Engineered Lactococcus lactis, for example, has been administered intragastrically for delivering polypeptides such as trefoil factors and interleukin-10 locally to intestinal/mucosal tissues. See Steidler et al. 2000 and Huyghebaert et al. 2005. However, a systemic increase in polypeptides delivered via Lactococcus lactis was not found.
Other types of genetically engineered bacteria have been used as vehicles for delivery of polypeptides to tumors in the body. An engineered Bifidobacterium strain, for example, has been shown to translocate from the gastrointestinal tract after oral administration and target to, replicate in, and express genes within tumors. See Cronin et al. 2010. This effect, however, depends on the unique ability of the Bifidobacterium to translocate from the gastrointestinal tract to extra-intestinal sites in the body. While Bifidobacterium may serve as a useful delivery vehicle for some purposes, the systemic distribution of the Bifidobacterium is potentially deleterious in certain subject populations such as immunocompromised patients.
Engineered bacteria capable of being administering into the gastrointestinal tract and delivering polypeptides in the bloodstream without systemic levels of the bacteria themselves being increased are needed.